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Updated: Oct 5, 2025
09:19
Improved 3D Hydrogel Cultures of Primary Glial Cells for In Vitro Modelling of Neuroinflammation
Published on: December 8, 2017
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ASK1 signaling regulates phase-specific glial interactions during neuroinflammation
Xiaoli Guo1, Atsuko Kimura1, Kazuhiko Namekata1
1Visual Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.
Summary
Glial apoptosis signal-regulating kinase 1 (ASK1) drives neuroinflammation in experimental autoimmune encephalomyelitis (EAE). Targeting ASK1 in microglia and astrocytes may reduce neuroinflammation in neurodegenerative diseases.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Neuroinflammation is a hallmark of neurodegenerative diseases.
- Apoptosis signal-regulating kinase 1 (ASK1) is implicated in neuroinflammation, but its specific roles are unclear.
Purpose of the Study:
- To investigate the cell-type-specific roles of ASK1 in neuroinflammation during experimental autoimmune encephalomyelitis (EAE).
- To elucidate the molecular mechanisms by which ASK1 contributes to EAE pathogenesis.
Main Methods:
- Generated conditional knockout (CKO) mice lacking ASK1 in specific immune and glial cells (T cells, dendritic cells, microglia/macrophages, astrocytes).
- Assessed EAE severity and neuroinflammation in ASK1 CKO mice.
- Utilized CX3CR1 system for microglia-specific ASK1 deletion.
Main Results:
- Microglia/macrophage-specific ASK1 deletion reduced neuroinflammation in early and late EAE stages.
- Astrocyte-specific ASK1 deletion ameliorated late-stage neuroinflammation.
- ASK1 in microglia/macrophages promotes a proinflammatory environment, activating astrocytes.
- Activated astrocytes, via ASK1, produce CCL2, further recruiting microglia/macrophages.
Conclusions:
- ASK1 exhibits cell-type-specific and phase-specific roles in EAE pathophysiology.
- ASK1-dependent interactions between microglia and astrocytes drive neuroinflammation.
- Glial ASK1 is a potential therapeutic target for neuroinflammation.
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